Intermediate Progenitor cells provide a transition between hematopoietic progenitors and their differentiated descendants

Abstract

AbstractGenetic and genomic analysis in Drosophila suggests that hematopoietic progenitors likely transition into terminal fates via intermediate progenitors (IPs) with some characteristics of either, but perhaps maintaining IP-specific markers. In the past, IPs have not been directly visualized and investigated due to lack of appropriate genetic tools. Here we report a split-GAL4 construct, CHIZ-GAL4, that identifies IPs as cells physically juxtaposed between true progenitors and differentiating hemocytes. IPs comprise a distinct cell type with a unique cell-cycle profile and they remain multipotent for all blood cell fates. Additionally, through their dynamic control of the Notch ligand, Serrate, IPs specify the fate of direct neighbors. The Ras pathway controls the number of IP cells and promotes their transition into differentiating cells. The split-GAL4 strategy is amenable for adoption in mammalian systems and would be invaluable in assigning trajectories that stem and progenitor populations follow as they develop into mature blood cells.